Cardiac Effects of Dexamethasone in Premature Infants

Dexamethasone is used to treat bronchopulmonary dysplasia in premature infants. Previous studies indicate this drug may produce ventricular dysfunction and cardiomyopathy during a 6 week course of therapy (Bensky et al., Pediatrics,97;1996). We studied the incidence, characteristics, and potential mechanisms for cardiac dysfunction in infants receiving dexamethasone (JCMC IRB#95-13). We also studied the effects of dexamethasone on contractions in human cardiac myocyte clusters (ETSU IRB#97-076e). Patients were hospitalized in the newborn intensive care unit at Johnson City Medical Center between April 1995 and February 1998 (n=37). Gestational age was 26±2.5 weeks (mean±SD), and birthweight was 842±318 grams. We initially administered dexamethasone at 0.5 mg/kg/day, and tapered over 23.6±11.7 days. Changes in ventricular function, dimensions, and wall thicknesses were measured with echocardiograms. Systemic blood pressures were measured by cuff, or using arterial lines when available. Evidence for glucose intolerance was determined by elevated serum glucose levels. Myocyte clusters (n=5, from 3 hearts), were obtained by enzymatically digesting cardiac pathologic specimens from 8-9 weeks gestation human fetuses. The clusters, contracted spontaneously and responded to field-stimulation after 12-24 h in enriched culture media. The myocyte clusters were bathed in normal Tyrode\u27s solution, and dexamethasone was administered in 1, 5, 10, 20 and 45 μM concentrations. Contractions were measured using a video edge detector. Cardiomyopathy developed in 24 of 37 patients receiving dexamethasone (64.9%), and was observed in patients receiving ≥ 14 days of therapy. The incidence of systemic hypertension and glucose intolerance was similar in patients with and without cardiomyopathy. Contractions in cardiac myocyte clusters decreased after 20 μM and 45 μM dexamethasone, but returned to baseline after rinsing the clusters with dexamethasone-free Tyrodes solution. There is a high incidence of cardiomyopathy in premature infants treated for bronchopulmonary dysplasia with ≥ 14 days of dexamethasone. The cardiomyopathy is not related to elevated systemic arterial pressures or blood glucose. In myocyte clusters from immature fetal hearts, contractions decrease after acute exposure to dexamethasone, but the decrease is reversible